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Study: Psychedelics can promote neural plasticity in the prefrontal cortex and expand pathways for mental health

– Cred­it: Cell Reports 2018 23, 3170–3182DOI: (10.1016/j.celrep.2018.05.022). Copy­right © 2018 The Authors

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Psy­che­delics in Neu­rol­o­gy: Poten­tial for Improv­ing Neu­ro­plas­tic­i­ty (Neu­rol­o­gy­Times):

Back in the 1950s, research was prov­ing that psy­che­del­ic agents could be effec­tive in the treat­ment of var­i­ous neu­ropsy­chi­atric dis­or­ders. Unfor­tu­nate­ly, just as sci­ence was explor­ing their ben­e­fi­cial effects, the coun­ter­cul­ture was explor­ing and embrac­ing their effects. Slow­ly but sure­ly, psy­che­delics were asso­ci­at­ed with rebel­lious youth and the tumul­tuous anti-war move­ment. As a result, the gov­ern­ment shut down most of the research.

The 1990s saw renewed inter­est in psy­che­del­ic com­pounds as a means to address neu­ropsy­chi­atric dis­or­ders. Research explored the ben­e­fits of MDMA and ket­a­mine to treat mood dis­or­ders and post­trau­mat­ic stress dis­or­der. Now, a new study sheds even more light on the promise these agents might pro­vide.

Neu­rol­o­gy Times invit­ed cor­re­spond­ing author David E Olson, PhD, to dis­cuss the study, “Psy­che­delics Pro­mote Struc­tur­al and Func­tion­al Neur­al Plas­tic­i­ty,” which appeared in the June issue of Cell Reports…

NT: What should clin­i­cians take away from this research? What does this mean for the field?

Dr Olson: I’m hope­ful that mod­ern research on ket­a­mine and psy­che­delics will lead to new and more effec­tive strate­gies for treat­ing mood and anx­i­ety dis­or­ders that involve pro­mot­ing neur­al plas­tic­i­ty in the pre­frontal cor­tex. We have to think of depres­sion and relat­ed dis­eases as dis­or­ders of neur­al cir­cuits rather than “chem­i­cal imbal­ances.” Plas­tic­i­ty-pro­mot­ing com­pounds are one pos­si­ble method for repair­ing the cir­cuits that are dam­aged in dis­eases like depres­sion and post­trau­mat­ic stress dis­or­der.”

The Study:

Psy­che­delics Pro­mote Struc­tur­al and Func­tion­al Neur­al Plas­tic­i­ty (Cell Reports). From the abstract:

  • Atro­phy of neu­rons in the pre­frontal cor­tex (PFC) plays a key role in the patho­phys­i­ol­o­gy of depres­sion and relat­ed dis­or­ders. The abil­i­ty to pro­mote both struc­tur­al and func­tion­al plas­tic­i­ty in the PFC has been hypoth­e­sized to under­lie the fast-act­ing anti­de­pres­sant prop­er­ties of the dis­so­cia­tive anes­thet­ic ket­a­mine. Here, we report that, like ket­a­mine, sero­ton­er­gic psy­che­delics are capa­ble of robust­ly increas­ing neu­ri­to­ge­n­e­sis and/or spin­o­gen­e­sis both in vit­ro and in vivo. These changes in neu­ronal struc­ture are accom­pa­nied by increased synapse num­ber and func­tion, as mea­sured by flu­o­res­cence microscopy and elec­tro­phys­i­ol­o­gy. The struc­tur­al changes induced by psy­che­delics appear to result from stim­u­la­tion of the TrkB, mTOR, and 5-HT2A sig­nal­ing path­ways and could pos­si­bly explain the clin­i­cal effec­tive­ness of these com­pounds. Our results under­score the ther­a­peu­tic poten­tial of psy­che­delics and, impor­tant­ly, iden­ti­fy sev­er­al lead scaf­folds for med­i­c­i­nal chem­istry efforts focused on devel­op­ing plas­tic­i­ty-pro­mot­ing com­pounds as safe, effec­tive, and fast-act­ing treat­ments for depres­sion and relat­ed dis­or­ders.

The Study in Context:

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